Cancer is a major cause of death worldwide. Colorectal cancer is the third most common form of cancer that affects people's life and health. In China, the rising incidence of colorectal cancer relates to the improving quality of life in recent years. The risk factors for colorectal cancer development include dietary factors such as high fat, high protein, and low fibers diet, overweight, smoking, and the sedentary life style. Cancer chemoprevention and chemotherapy concern methods and agents that reduce the incidence or delay the onset of specific forms of cancer. The development of chemoprevention and chemotherapy strategies for cancer, such as colorectal cancer, requires effective methods for screening, identifying, and monitoring effect of cancer chemoprevention and chemotherapy methods and agents.
Epidemiological studies are currently used for evaluating, charactering, and monitoring the effects of cancer chemoprevention strategies. These methods often require large cohorts of population to whom one or more potential cancer chemoprevention methods or agents are given for 10 to 20 years of prolonged follow-ups. These methods often have perspective endpoints at which the incidence of cancer may be significantly reduced as compared to that in the subjects in control cohorts who do not receive cancer chemoprevention methods or agents. These longitudinal cohort studies are time-consuming and costly making them unrealistic for screening, identification, and monitoring candidate methods and agents for cancer chemoprevention and chemotherapy.
Some carcinogens can induce a large amount of aberrant crypt foci (ACF) in rats, such as azoxymethane (AOM) and 1,2-dimethylhydrazine (DMH). The presence of ACF may be the earliest pathological change in the development of colorectal cancer in rodents and humans (Shimizu et al. Cancer Lett, 1:135-142, 2006). The intervention of cancer chemoprevention agents in this rodent model reduces the number of ACF. This ACF-based rat model provides one method for identifying and characterizing agents for anti-cancer effects, including in colorectal cancer. However, these methods use invasive procedures involving euthanasia of model animals, such as rats and mice, and staining of gastrointestinal tract with methylene blue to determine the number of ACF before and after treatment with anti-cancer agents.
In 1995, Moor et al. recognized that the microbial compositions differed significantly in populations at high and low risk of colorectal cancer (Moor et al., Intestinal Floras of Populations That Have a High Risk of Colon Cancer, Applied and Environmental Microbiology 9:3202-3207, 1995). Approximately 500 species or 1014 the number of microorganisms live in the intestinal tract of host animals; and the microbial composition in fecal flora relates to the composition in gut flora. However, the composition of cultured fecal flora often differs from the composition in gut flora because, depending on the culture condition, certain microbial species may overgrowth whereas other certain microbial species may not grow, which often results in alterations of the microbial composition of the cultured fecal flora.
There exists a need for methods for detecting and monitoring the therapeutic effects of an anti-cancer agent that are noninvasive, efficient, and accurate. The present invention seeks to fulfill these needs and provides further related advantages.